Multidimensional regulation of the opioid network by ACKR3

Endogenous opioid peptides and prescription opioid drugs modulate pain, anxiety and stress by activating four classical opioid receptors (MOR, DOR,KOR and NOP). The laboratory of Immuno-Pharmacology and Interactomics has recently identified a new broad-spectrum opioid receptor:ACKR3/CXCR7, hitherto known as atypical scavenger receptor for chemokines. In contrast to classical opioid receptors, ACKR3 is a non-signalling receptor with unique scavenging functions for opioid peptides produced in the central nervous system, reducing their availability and signalling through the classical opioid receptors. The expansion of the opioid receptor family by a new non-signalling member with original regulatory functions adds an unforeseen dimension of fine-tuning to the opioid system but also opens promising alternative strategies for therapeutic intervention in opioid-related disorders, which is particularly timely in the context of the opioid crisis: This project aims to get a better understanding of the multidimensional regulatory roles that ACKR3 exerts on the opioid network.